Section Toxicology and Biomedical Sciences, C.R. ENEA Casaccia, Via Anguillarese 301, 00123 Rome, Italy.
J Cancer Res Clin Oncol. 2010 Jul;136(7):1101-9. doi: 10.1007/s00432-009-0757-3. Epub 2010 Jan 13.
Human papillomavirus (HPV) infection is considered the major cause of cervical cancer (CC), but a number of infected women do not develop invasive lesions, suggesting the role of genetic susceptibility and environmental co-factors for cancer outbreak. The aim of this study was to investigate whether some GST polymorphisms could influence the risk to develop CC, either by themselves or in combination with smoking habit, in a cohort of high-risk HPV (HR-HPV) infected Italian women.
The study population comprises 192 Italian women including 81 HR-HPV infected women bearing cervical lesions and 111 healthy controls. The cases include: 26 low-grade squamous intraepithelial lesions (LSILs), 30 high-grade-SIL, and 25 CCs, while controls were all negative for HPV. DNA was extracted from peripheral blood samples or cytobrush and individuals were genotyped for GSTM1, GSTT1, and GSTP1 polymorphisms using PCR and PCR/RFLP techniques.
On studying the association of GSTs gene polymorphisms with cervical cancer lesions, the combination of GSTM1 null, GSTT1 null and GSTP1 AA genotypes, independently on smoking habit, seems to be related to a 5.7-fold increased risk of developing CLs with a considerable statistical significance (P = 0.0091).
We suggest that the investigation of multiple gene polymorphisms, versus single genes, could contribute to a better understanding of the effect of susceptibility genes on cancer risk.
人乳头瘤病毒（HPV）感染被认为是宫颈癌（CC）的主要原因，但许多感染的女性并未发展为侵袭性病变，这表明遗传易感性和环境共同因素在癌症发生中的作用。本研究旨在调查某些 GST 多态性是否会影响 HPV 高危（HR-HPV）感染的意大利女性发生 CC 的风险，无论是单独作用还是与吸烟习惯共同作用。
该研究人群包括 192 名意大利女性，其中 81 名 HR-HPV 感染的女性伴有宫颈病变，111 名健康对照。病例包括：26 例低度鳞状上皮内病变（LSILs）、30 例高度鳞状上皮内病变（HSIL）和 25 例 CC，而对照组均为 HPV 阴性。从外周血样本或宫颈刷中提取 DNA，并用 PCR 和 PCR/RFLP 技术对 GSTM1、GSTT1 和 GSTP1 多态性进行基因分型。
在研究 GSTs 基因多态性与宫颈癌病变的相关性时，GSTM1 缺失、GSTT1 缺失和 GSTP1 AA 基因型的组合，独立于吸烟习惯，似乎与发生 CLs 的风险增加 5.7 倍相关，具有显著的统计学意义（P = 0.0091）。
我们认为，与单一基因相比，对多个基因多态性的研究可能有助于更好地理解易感性基因对癌症风险的影响。
